The control of the inflammatory response induced by the implantation of foreign
biomaterials is fundamental in determining tissue healing. It has been shown that the activation of specific macrophage pathways upon contact with a
biomaterial can lead either to a chronic
inflammation preventing a physiological tissue repair or to an improved tissue healing. In the case of bone repair,
calcium phosphate cements with good osteoconductivity properties have been successfully applied in bone defect filling and repair, but poor handling properties, insufficient viscous flow and unmatched degradation rate are still problems that remain unsolved. In this study, a
strontium-doped
hydroxyapatite (HA) gel was modified by integrating branched poly(epsilon-
lysine)
dendrons with third-generation branches exposing
phosphoserine (SrHA/G3-K PS). The interaction of this material with macrophages was investigated in vitro, focusing on the secretion and gene expression of specific pro-inflammatory
cytokines. Our results showed that the addition of
strontium and G3-K PS to HA
sol-gel could down-regulate the gene expression of inflammatory factors such as IL-1β, TNF-α and MCP-1, while increasing the gene expression of
IL-6, a
cytokine known for its osteogenic effect. These results were further confirmed by ELISA test of the respective
protein concentrations. When exposed to supernatants of macrophage culture in the presence of
strontium and G3-K PS, osteoblast viability was promoted with elevated osteogenic gene markers, in terms of OPG, ALP, OCN and COL-I. In vivo implantation experiments using an osteoporotic rat model with bone defect further confirmed that the addition of G3-K PS to HA could dramatically promote new bone regeneration. Although the introduction of
strontium improved the degradation properties of the
injectable materials, no positive effect on promoting in vivo bone regeneration was observed.